NM_020344.4:c.1256G>C

Variant names:

• chr9-19573442-C-G
• rs1476444331
• NM_020344.4:c.1256G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020344.4(SLC24A2):​c.1256G>C​(p.Ser419Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC24A2 NM_020344.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68
• Publications: 0 publications found

Genes affected

SLC24A2 (HGNC:10976): (solute carrier family 24 member 2) This gene encodes a member of the calcium/cation antiporter superfamily of transport proteins. The encoded protein belongs to the SLC24 branch of exchangers, which can mediate the extrusion of one Ca2+ ion and one K+ ion in exchange for four Na+ ions. This family member is a retinal cone/brain exchanger that can mediate a light-induced decrease in free Ca2+ concentration. This protein may also play a neuroprotective role during ischemic brain injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1632399).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020344.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A2	NM_020344.4	MANE Select	c.1256G>C	p.Ser419Thr	missense	Exon 7 of 11	NP_065077.1	Q9UI40-1
	SLC24A2	NM_001375850.1		c.1256G>C	p.Ser419Thr	missense	Exon 7 of 11	NP_001362779.1	Q9UI40-1
	SLC24A2	NM_001193288.3		c.1205G>C	p.Ser402Thr	missense	Exon 6 of 10	NP_001180217.1	Q9UI40-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A2	ENST00000341998.7	TSL:1 MANE Select	c.1256G>C	p.Ser419Thr	missense	Exon 7 of 11	ENSP00000344801.1	Q9UI40-1
	SLC24A2	ENST00000286344.4	TSL:1	c.1205G>C	p.Ser402Thr	missense	Exon 6 of 10	ENSP00000286344.3	Q9UI40-2
	SLC24A2	ENST00000903169.1		c.1256G>C	p.Ser419Thr	missense	Exon 7 of 11	ENSP00000573228.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151220 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458716 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725754

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39280

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110190

Other (OTH) AF: 0.00 AC: 0 AN: 60138

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151220 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73768

African (AFR) AF: 0.00 AC: 0 AN: 41040

American (AMR) AF: 0.000132 AC: 2 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5106

South Asian (SAS) AF: 0.00 AC: 0 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.77
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.13
Sift	Benign	0.50	T
Sift4G	Benign	0.53	T
Polyphen		0.0070	B
Vest4		0.43
MutPred		0.14		Gain of glycosylation at T418 (P = 0.0724)
MVP		0.85
MPC		0.096
ClinPred		0.34	T
GERP RS		4.1
Varity_R		0.096
gMVP		0.36
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1476444331; hg19: chr9-19573440;